1. Field of the Invention
The present invention relates generally to the fields of molecular biology of vectors and gene therapy. More specifically, the present invention relates to a chimeric adenoviral vector system and methods for its use.
2. Description of the Related Art
A number of gene therapy strategies for diseases of the heart, lung, and blood are based upon stable genetic modification of relevant parenchymal cells. In many contexts, this can be only achieved by direct in vivo gene delivery whereby stable transduction is achieved in situ. To this end, a variety of viral vectors have been developed to exploit their integrative capacity as a means to achieve stable genetic transduction. Vectors of this type include recombinant retroviruses and adeno-associated viruses (AAV) and have been employed in ex vivo gene transfer schemes to achieve stable genetic modification of target cells.
Despite the utility of retroviral and AAV vectors in these ex vivo contexts, employment of these vectors for direct in vivo gene delivery has been problematic. In this regard, issues of effective titer and in vivo stability have limited the utility of these vectors for the many schemes whereby direct in situ transduction of a parenchyma is required. On the other hand, recombinant adenoviral vectors can be prepared to high titer, and possess in vivo stability, both factors which have allowed their employment for direct in vivo gene delivery to differentiated target cells. The limitation of adenoviral vectors, however, is that the derived heterologous gene expression is only transient. This is based, in part, upon the fact that adenoviral vector transduced cells are immunologically eradicated by the host. In addition, the parent adenovirus lacks the capacity to integrate its genome in the host chromosome.
The prior art is deficient in the lack of effective vector system which allows stable genetic modification of cells after direct in vivo vector administration. The present invention fulfills this longstanding need and desire in the art.